PMID- 21214269
OWN - NLM
STAT- MEDLINE
DCOM- 20110613
LR  - 20211020
IS  - 1535-3907 (Electronic)
IS  - 1535-3893 (Print)
IS  - 1535-3893 (Linking)
VI  - 10
IP  - 3
DP  - 2011 Mar 4
TI  - Analysis of phosphotyrosine signaling in glioblastoma identifies STAT5 as a novel 
      downstream target of DeltaEGFR.
PG  - 1343-52
LID - 10.1021/pr101075e [doi]
AB  - An in-frame deletion mutation in Epidermal Growth Receptor (EGFR), DeltaEGFR is a 
      common and potent oncogene in glioblastoma (GBM), promoting growth and survival 
      of cancer cells. This mutated receptor is ligand independent and constitutively 
      active. Its activity is low in intensity and thought to be qualitatively 
      different from acutely ligand stimulated wild-type receptor implying that the 
      preferred downstream targets of DeltaEGFR play a significant role in malignancy. To 
      understand the DeltaEGFR signal, we compared it to that of a kinase-inactivated 
      mutant of DeltaEGFR and wild-type EGFR with shotgun phosphoproteomics using an 
      electron-transfer dissociation (ETD) enabled ion trap mass spectrometer. We 
      identified and quantified 354 phosphopeptides corresponding to 249 proteins. 
      Among the DeltaEGFR-associated phosphorylations were the previously described Gab1, 
      c-Met and Mig-6, and also novel phosphorylations including that of STAT5 on 
      Y694/9. We have confirmed the most prominent phosphorylation events in cultured 
      cells and in murine xenograft models of glioblastoma. Pathway analysis of these 
      proteins suggests a preference for an alternative signal transduction pathway by 
      DeltaEGFR compared to wild-type EGFR. This understanding will potentially benefit the 
      search for new therapeutic targets for DeltaEGFR expressing tumors.
FAU - Chumbalkar, Vaibhav
AU  - Chumbalkar V
AD  - Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas 77030, USA.
FAU - Latha, Khatri
AU  - Latha K
FAU - Hwang, YeoHyeon
AU  - Hwang Y
FAU - Maywald, Rebecca
AU  - Maywald R
FAU - Hawley, Lauren
AU  - Hawley L
FAU - Sawaya, Raymond
AU  - Sawaya R
FAU - Diao, Lixia
AU  - Diao L
FAU - Baggerly, Keith
AU  - Baggerly K
FAU - Cavenee, Webster K
AU  - Cavenee WK
FAU - Furnari, Frank B
AU  - Furnari FB
FAU - Bogler, Oliver
AU  - Bogler O
LA  - eng
GR  - P01 CA095616-09/CA/NCI NIH HHS/United States
GR  - R01CA108500/CA/NCI NIH HHS/United States
GR  - P01 CA095616/CA/NCI NIH HHS/United States
GR  - CA016672/CA/NCI NIH HHS/United States
GR  - P50CA127001/CA/NCI NIH HHS/United States
GR  - R01 CA108500/CA/NCI NIH HHS/United States
GR  - P30 CA016672-27/CA/NCI NIH HHS/United States
GR  - P50 CA127001-04/CA/NCI NIH HHS/United States
GR  - P30 CA016672/CA/NCI NIH HHS/United States
GR  - R01 CA108500-06/CA/NCI NIH HHS/United States
GR  - P50 CA127001/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110214
PL  - United States
TA  - J Proteome Res
JT  - Journal of proteome research
JID - 101128775
RN  - 0 (Phosphopeptides)
RN  - 0 (STAT5 Transcription Factor)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - ErbB Receptors/*genetics/*metabolism
MH  - Glioblastoma/*metabolism
MH  - Humans
MH  - Mice
MH  - Mice, Nude
MH  - Mutation
MH  - Neoplasm Transplantation
MH  - Neoplasms/genetics/metabolism
MH  - Phosphopeptides/analysis
MH  - Phosphotyrosine/*metabolism
MH  - STAT5 Transcription Factor/*metabolism
MH  - Signal Transduction/*physiology
MH  - Tandem Mass Spectrometry/methods
PMC - PMC3049961
MID - NIHMS266451
EDAT- 2011/01/11 06:00
MHDA- 2011/06/15 06:00
PMCR- 2012/03/04
CRDT- 2011/01/11 06:00
PHST- 2011/01/11 06:00 [entrez]
PHST- 2011/01/11 06:00 [pubmed]
PHST- 2011/06/15 06:00 [medline]
PHST- 2012/03/04 00:00 [pmc-release]
AID - 10.1021/pr101075e [doi]
PST - ppublish
SO  - J Proteome Res. 2011 Mar 4;10(3):1343-52. doi: 10.1021/pr101075e. Epub 2011 Feb 
      14.